Location
Philadelphia, PA
Start Date
17-4-2026 1:30 PM
End Date
17-4-2026 2:30 PM
Description
Introduction: Timely reperfusion of the heart to restore blood flow and oxygen is critical to rescue ischemic myocardium in the setting of myocardial infarction and reduce cardiac morbidity and mortality. However, reperfusion following prolonged ischemic injury exhibits salvaging, but paradoxically, additional cellular damage, contributing to a larger infarct size. Termed ischemia-reperfusion injury (IRI), the myocardium undergoes various pathophysiological changes following reperfusion – such as apoptosis, oxidative stress, and mitochondrial dysfunction – thus exacerbating cellular damage and death caused by ischemic injury. The research on attenuation of IRI is critical to maximize the benefit of reperfusion. Spermidine is a natural polyamine with anti-inflammatory and antioxidant properties. This project aims to investigate the cardioprotective effects of spermidine in an ex-vivo IRI model.
Methods: Hearts were isolated from heparinized male Sprague-Dawley rats and mounted onto the Langendorff apparatus. After establishing the stable baselines, hearts were initiated with global ischemia by stopping Krebs buffer perfusion for 35 minutes, followed by reperfusion of Krebs buffer for 45 minutes (35I-45R). Cardiac function parameters - heart rate (HR), left ventricular end systolic pressure (LVESP), left ventricular end diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), and maximal rate of rise of LVESP (dP/dt max) - were recorded before and during 35I-45R. At the end of the recording, hearts were frozen and sectioned for infarct size determination by using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Spermidine (500 µM) was infused to hearts without IRI to evaluate spermidine’s effects on cardiac function. Additionally, spermidine (200 µM and 500 µM) was infused to hearts for 10 minutes either before ischemia (pretreatment) or at the beginning of reperfusion (posttreatment) to evaluate its effects on IRI. By contrast, nontreated IRI hearts were infused with Krebs buffer in the absence of spermidine with the aforementioned parameters. Data was expressed with mean±SE and effects were compared to nontreated IRI hearts.
Results: Nontreated IRI hearts exhibited a 32.36±0.02% (n=4) infarct. Posttreatment hearts with spermidine infusion of 200 µM and 500 µM concentrations yielded 28.20% (n=1) and 34.55±0.01% (n=2) infarct, respectively. Pretreatment hearts with spermidine infusion of 200 µM and 500 µM concentrations yielded 26.02±0.05% (n=5) and 23.67±0.04% (n=5) infarct, respectively. Perfusion of spermidine (500 µM, n=4) for 45 minutes had similar cardiac function as baselines. By contrast, nontreated IRI hearts showed a compromised cardiac function at the end of reperfusion. They exhibited a higher LVEDP (64.13±7.43 mmHg) and lower LVDP (37.24±10.44 mmHg) and dP/dt max (801.95±189.83 mmHg/sec) when compared to the baselines (LVEDP: 8.23±0.36 mmHg; LVDP: 82.02±2.28 mmHg; dP/dtmax: 2089.77±84.27 mmHg/sec). Spermidine pretreatment and posttreatment did not improve IRI-associated cardiac function parameters when compared to those of nontreated IRI hearts.
Conclusion: Preliminary data suggests that infusion of spermidine alone shows minimal disturbance on the normal cardiac function. Additionally, nontreated IRI control compromises cardiac function accompanied by a larger infarct size. Conversely, spermidine pretreatment, not posttreatment, exerts mild salvage of infarct percentage without improvement of cardiac function. Future studies would focus on optimization of spermidine pretreatment in IRI and elucidation of the underlying mechanisms.
Embargo Period
6-3-2026
Included in
Cardioprotective role of spermidine in ischemia-reperfusion injury
Philadelphia, PA
Introduction: Timely reperfusion of the heart to restore blood flow and oxygen is critical to rescue ischemic myocardium in the setting of myocardial infarction and reduce cardiac morbidity and mortality. However, reperfusion following prolonged ischemic injury exhibits salvaging, but paradoxically, additional cellular damage, contributing to a larger infarct size. Termed ischemia-reperfusion injury (IRI), the myocardium undergoes various pathophysiological changes following reperfusion – such as apoptosis, oxidative stress, and mitochondrial dysfunction – thus exacerbating cellular damage and death caused by ischemic injury. The research on attenuation of IRI is critical to maximize the benefit of reperfusion. Spermidine is a natural polyamine with anti-inflammatory and antioxidant properties. This project aims to investigate the cardioprotective effects of spermidine in an ex-vivo IRI model.
Methods: Hearts were isolated from heparinized male Sprague-Dawley rats and mounted onto the Langendorff apparatus. After establishing the stable baselines, hearts were initiated with global ischemia by stopping Krebs buffer perfusion for 35 minutes, followed by reperfusion of Krebs buffer for 45 minutes (35I-45R). Cardiac function parameters - heart rate (HR), left ventricular end systolic pressure (LVESP), left ventricular end diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), and maximal rate of rise of LVESP (dP/dt max) - were recorded before and during 35I-45R. At the end of the recording, hearts were frozen and sectioned for infarct size determination by using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Spermidine (500 µM) was infused to hearts without IRI to evaluate spermidine’s effects on cardiac function. Additionally, spermidine (200 µM and 500 µM) was infused to hearts for 10 minutes either before ischemia (pretreatment) or at the beginning of reperfusion (posttreatment) to evaluate its effects on IRI. By contrast, nontreated IRI hearts were infused with Krebs buffer in the absence of spermidine with the aforementioned parameters. Data was expressed with mean±SE and effects were compared to nontreated IRI hearts.
Results: Nontreated IRI hearts exhibited a 32.36±0.02% (n=4) infarct. Posttreatment hearts with spermidine infusion of 200 µM and 500 µM concentrations yielded 28.20% (n=1) and 34.55±0.01% (n=2) infarct, respectively. Pretreatment hearts with spermidine infusion of 200 µM and 500 µM concentrations yielded 26.02±0.05% (n=5) and 23.67±0.04% (n=5) infarct, respectively. Perfusion of spermidine (500 µM, n=4) for 45 minutes had similar cardiac function as baselines. By contrast, nontreated IRI hearts showed a compromised cardiac function at the end of reperfusion. They exhibited a higher LVEDP (64.13±7.43 mmHg) and lower LVDP (37.24±10.44 mmHg) and dP/dt max (801.95±189.83 mmHg/sec) when compared to the baselines (LVEDP: 8.23±0.36 mmHg; LVDP: 82.02±2.28 mmHg; dP/dtmax: 2089.77±84.27 mmHg/sec). Spermidine pretreatment and posttreatment did not improve IRI-associated cardiac function parameters when compared to those of nontreated IRI hearts.
Conclusion: Preliminary data suggests that infusion of spermidine alone shows minimal disturbance on the normal cardiac function. Additionally, nontreated IRI control compromises cardiac function accompanied by a larger infarct size. Conversely, spermidine pretreatment, not posttreatment, exerts mild salvage of infarct percentage without improvement of cardiac function. Future studies would focus on optimization of spermidine pretreatment in IRI and elucidation of the underlying mechanisms.